The essential role of vitamin A (VA) in growth and development is undisputed, but mechanisms underlying its effects have not been fully elucidated. Available data indicate that VA influences growth at the level of cell proliferation, differentiation, maturation, and/or apoptosis through the actions of its oxidative derivative, RA, which binds to and activates nuclear receptor complexes that, in turn, regulate the transcription of genes that impact growth. VA-deficiency disrupts growth and tissue specification processes, which presumably occur due to a reduction in RA availability at the cellular level,. This interpretation is supported by (a) studies showing that supplementation of VA-deficient systems with RA rescues the pathology when the system has the capacity to generate new cells, for example, embryos, but does not rescue the system if it is incapable of generating new cells, for example, photoreceptor cells in adult rats, and (b) studies showing that supplementation of VA-sufficient systems with excess RA causes growth-related deformations and structural duplications. While VA likely has pleiotropic effects on complex animal systems, it is nonetheless reasonable to conclude that among its primary functions is its role as a source of RA for RA-mediated tissue morphogenetic and cell development processes. Consistent with this expectation, the principal investigator has shown that RA is present in VA-sufficient postnatal rat olfactory tissue and is below the level of detection in VA-deficient olfactory tissue, and this decreased availability of RA is accompanied by increased basal cell proliferation and decreased numbers of mature olfactory neurons in the olfactory epithelium (OE). These results lend support to the working hypothesis that RA signaling mediates neurogenesis in vivo. To further elucidate the role of VA status and/or RA signaling in effecting neuron development in vivo, the PI proposes to localize expression of nuclear receptors in the postnatal olfactory organ, localize RA sensitive sites in the olfactory organ, and study the effects of VA in mice whose VA status is compromised either through dietary or genetic manipulation.